BACKGROUND/AIMS: It is well documented that levels of plasma non-transferrin-bound iron (NTBI), a particularly toxic form of iron, are increased in iron overload disorders. In light of the pathogenetic importance of NTBI in chronic iron overload, we have studied the ability of new orally active iron chelators to promote the biliary excretion of iron originating as plasma 55Fe-NTBI. METHODS: Biliary iron kinetics of plasma 55Fe-labeled NTBI and cumulative recoveries of 55Fe in bile were determined in normal and carbonyl iron-loaded rats receiving a single intragastric dose of iron chelator. These chelators were the novel hydroxypyridin-4-one compounds CP102, CP41, and their respective pro-drugs CP117 and CP165. RESULTS: The cumulative recovery of 55Fe in bile of normal rats was increased by 5.2-, 7.9-, 11.5-, and 9.2-fold with CP102, CP117, CP41 and CP165, respectively. In iron overloaded rats, these compounds increased the cumulative recovery by 28.6-, 48.6-, 72.6-, and 32-fold, respectively. All the chelators had a choleretic effect, were metabolized by the liver as demonstrated by HPLC study of bile, and were not cytotoxic since normal plasma transaminase levels were maintained at the end of the experiments. CONCLUSIONS: These chelators have potential interest for the treatment of iron overload conditions and may offer advantages over simple N-alkyl-hydroxypyridinones such as deferiprone (CP20, L1).

Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary excretion of plasma non-transferrin-bound iron in rats / Giuliana, Zanninelli; R., Choundry; Oliver, Loreal; Dominique, Guyader; Gérard, Lescoat; Josiane, Arnaud; Verna, Roberto; Bertrand, Cosson; Surinder, Singh; C. R., Hider; Pierre, Brissot. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - STAMPA. - 27:1(1997), pp. 176-184. [10.1016/s0168-8278(97)80299-1]

Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary excretion of plasma non-transferrin-bound iron in rats

VERNA, Roberto;
1997

Abstract

BACKGROUND/AIMS: It is well documented that levels of plasma non-transferrin-bound iron (NTBI), a particularly toxic form of iron, are increased in iron overload disorders. In light of the pathogenetic importance of NTBI in chronic iron overload, we have studied the ability of new orally active iron chelators to promote the biliary excretion of iron originating as plasma 55Fe-NTBI. METHODS: Biliary iron kinetics of plasma 55Fe-labeled NTBI and cumulative recoveries of 55Fe in bile were determined in normal and carbonyl iron-loaded rats receiving a single intragastric dose of iron chelator. These chelators were the novel hydroxypyridin-4-one compounds CP102, CP41, and their respective pro-drugs CP117 and CP165. RESULTS: The cumulative recovery of 55Fe in bile of normal rats was increased by 5.2-, 7.9-, 11.5-, and 9.2-fold with CP102, CP117, CP41 and CP165, respectively. In iron overloaded rats, these compounds increased the cumulative recovery by 28.6-, 48.6-, 72.6-, and 32-fold, respectively. All the chelators had a choleretic effect, were metabolized by the liver as demonstrated by HPLC study of bile, and were not cytotoxic since normal plasma transaminase levels were maintained at the end of the experiments. CONCLUSIONS: These chelators have potential interest for the treatment of iron overload conditions and may offer advantages over simple N-alkyl-hydroxypyridinones such as deferiprone (CP20, L1).
1997
bile; hydroxypyridinones; iron; iron overload; non-transferrin-bound iron; oral chelation; rat
01 Pubblicazione su rivista::01a Articolo in rivista
Novel orally active iron chelators (3-hydroxypyridin-4-ones) enhance the biliary excretion of plasma non-transferrin-bound iron in rats / Giuliana, Zanninelli; R., Choundry; Oliver, Loreal; Dominique, Guyader; Gérard, Lescoat; Josiane, Arnaud; Verna, Roberto; Bertrand, Cosson; Surinder, Singh; C. R., Hider; Pierre, Brissot. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - STAMPA. - 27:1(1997), pp. 176-184. [10.1016/s0168-8278(97)80299-1]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/86093
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